Abstract
Progressive cardiac dilatation and pump failure of unknown etiology
has been termed idiopathic dilated cardiomyopathy (DCM). During recent
years a large body of data has accumulated indicating that functionally
active antibodies or autoantibodies being able to recognize and to
stimulate the cardiac beta(1)-adrenergic receptor (anti-beta(1)-AR)
may play an important role in the initiation and/or clinical course
of DCM. Recent experiments in rats even point towards a cause-and-effect
relation between stimulatory anti-beta(1)-AR antibodies and DCM.
Immunization of rats against the second extracellular loop of the
human beta(1)-adrenergic receptor (100% sequence-identity between
human and rat) resulted in both development of stimulatory anti-beta(1)-AR
antibodies and development of progressive cardiac dilatation and
dysfunction. Isogenic transfer of stimulatory anti-beta(1)-AR from
cardiomyopathic into healthy inbred animals reproduced the disease,
hence providing conclusive proof for a beta(1)-receptor-directed
autoimmune attack as a possible cause of cardiomyopathy. This kind
of cardiomyopathy is now referred to as anti-beta(1)-AR-induced dilated
immune-cardiomyopathy (DiCM). The following article reviews recent
evidence obtained from experimental animal-models implying a significant
role of the cardiac beta(1)-adrenergic receptor as a pathophysiologically
and clinically relevant autoantigen also in human DCM.
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